Is perioperative fasting associated with complications, length of hospital stay and mortality among gastric and colorectal cancer patients? A cohort study

ABSTRACT BACKGROUND: During a surgical procedure, patients are often subjected to fasting for times that are more prolonged than the ideal, which may lead to complications. OBJECTIVE: To evaluate the duration of perioperative fasting and its association with postoperative complications, length of hospital stay (LOS) and mortality among gastric and colorectal cancer patients. DESIGN AND SETTING: Cohort study developed in a surgical oncology hospital in the city of Natal (Rio Grande do Norte, Brazil). METHODS: Patients aged over 18 years were included. The Clavien-Dindo surgical complication scale was used to evaluate occurrences of postoperative complications. LOS was defined as the number of days for which patients stayed in the hospital after surgery, or until the day of death. RESULTS: Seventy-seven patients participated (59.8 ± 11.8 years; 54.5% females; 70.1% with bowel tumor). The incidences of postoperative complications and death were 59.7% and 3.9%, respectively. The duration of perioperative fasting was 59.0 ± 21.4 hours, and it was higher among non-survivors and among patients with prolonged hospital stay (≥ 6 days). For each one-hour increase in the durations of perioperative and postoperative fasting, the odds of prolonged hospitalization increased by 12% (odds ratio, OR = 1.12; 95% confidence interval, CI 1.04-1.20) and 5% (OR = 1.05; 95% CI 1.02-1.08), respectively. CONCLUSION: Prolonged perioperative fasting, especially in the postoperative period, was observed in a sample of patients with gastric and colorectal cancer, and this was an independent predictor of LOS.

two hours before surgery, can bring benefits regarding glycemic and functional parameters. 6 It also reduces hospitalization and does not increase the aspiration risk among patients undergoing elective surgery. Thus, shortening of fasting contributes towards maintenance of nutritional status. 7 Despite the recommendations, implementation of these protocols is still only just beginning in many countries, including Brazil.
So far, a shortened perioperative fasting period for surgical cancer patients has not yet been studied.

OBJECTIVE
The objective of this study was to evaluate the duration of perioperative fasting and its association with postoperative complications, length of hospital stay (LOS) and mortality in a sample of surgical patients with gastric and colorectal cancer.

Design, sample and ethics
This was a prospective cohort study conducted between December was the presence of other diseases that cause a decrease in muscle mass, such as heart failure, acquired immunodeficiency syndrome, inflammatory bowel diseases, non-cancer liver diseases or tuberculosis. Patients undergoing palliative surgery (for whom only exploratory laparotomy and biopsy were performed) were also excluded because of their extensive disease verified during the surgery.
All subjects gave their written informed consent, in accordance with the Declaration of Helsinki.

Procedures
All patients with gastric and colorectal cancer who were scheduled to undergo a surgical oncological procedure during the study period was invited to participate. Before the surgical procedure, data to characterize the sample were collected from the patients' medical records and through in-person interviews: sex, age, ethnicity, presence of comorbidities (diabetes and/ or hypertension) and smoking, along with information about the tumor, any neoadjuvant treatment involving chemotherapy and/or radiotherapy that had been undertaken, and the individual's functional capacity in terms of the Eastern Cooperative Oncology Group Performance Status (ECOG-PS). 8 All patients were followed up for 30 days after the surgical procedure, regardless of the length of their hospital stay, or until the time of death. After the surgery, information about the duration and type of surgery performed, and about occurrences of postoperative complications, were collected.
Body mass index (BMI, kg/m 2 ) was calculated from height and weight. From this, the patients were classified as underweight, normal weight, overweight or obese, in accordance with the World Health Organization (WHO) criteria. 9 Nutritional status was also evaluated by means of the Patient-Generated Subjective Global Assessment (PG-SGA). Score A indicated a patient without malnutrition, while scores B and C represented malnourishment (suggestive of moderate malnutrition and severe malnutrition, respectively). 10 Fasting was considered to consist of absence of oral (food and drink), enteral or parenteral nutrition. Patients were asked directly what the duration of their fasting before and after surgery had been and confirmation of this was sought from the electronic records, whenever possible. Only when it was not possible to obtain reliable information regarding the duration of fasting from the patient was information from the medical records used.

Outcomes
The outcomes from this study comprised surgical complications, duration of hospitalization and incidence of hospital death. The Clavien-Dindo scale was used to evaluate surgical complications. 11 This classifies complications in ascending degrees, from I to V, according to their severity, and in our study the version of the scale translated and adapted for use in Brazilian Portuguese was used. 12 Based on other similar studies in the literature, [13][14][15] only complications classified as grade II onwards were considered in the present study. Grade II complications include infectious processes treated with antibiotics, need for blood transfusion and parenteral nutrition.
Complications of grades III, IV and V include surgical re-interventions for correction of fistulas, intra-abdominal abscess and evisceration, intensive care unit (ICU) hospitalizations for treatment of abdominal sepsis, and death. The LOS was defined as the number of days for which patients stayed at the hospital after surgery, or until the day of death.

Statistical analysis
Descriptive statistics were calculated and the data were expressed as the mean and standard deviation for quantitative parametric variables; as the median and interquartile range (P25-P75) for quantitative nonparametric variables; or as the absolute and relative frequency for categorical variables.
The normality of quantitative variables was assessed using the Kolmogorov-Smirnov test. Clinical and nutritional characteristics were compared between groups using the chi-square test for categorical variables and using the independent t test

RESULTS
A total of 140 patients were initially screened before surgery, but 63 of them were excluded because their data regarding the duration of pre or postoperative fasting were incomplete. Therefore, 77 patients of mean age 59.8 ± 11.8 years were enrolled in this study. Table 1 Table 2 shows the patients' clinical and nutritional features according to the cancer site. In general, gastric cancer patients had worse status performance and presented longer duration of surgery and more complications than did colorectal cancer patients. Also, LOS was greater among gastric cancer patients. Although the surgical complications differed between the groups, the time taken (in days) for complications to appear was not different.
The duration of fasting did not differ between patients with and without complications in the postoperative period, as demonstrated in Table 3. Survivors had shorter postoperative and perioperative fasting, in comparison with non-survivors. Patients with longer hospitalization after surgery had longer durations of fasting during the postoperative and perioperative period than patients with hospital stays after surgery shorter than six days.
Logistic regression was performed to evaluate the association between prolonged hospitalization after surgery (≥ 6 days) and the duration of perioperative or postoperative fasting ( Table 4). For each one-hour increase in the duration of perioperative fasting, the odds of prolonged hospitalization increased by 12%; while for each one-hour increase in the duration of postoperative fasting, it increased by 5%. In the multivariate analysis adjusted for confounders, the duration of perioperative or postoperative fasting was not an independent predictor of postoperative complications or death in the hospital. A onehour increase in the durations of postoperative and perioperative fasting increased the odds of death by 14% and 15%, respectively, but it did not reach statistical significance after adjustment for confounders.

DISCUSSION
The aim of the current study was to evaluate the duration of perioperative fasting and its association with postoperative complications, LOS and mortality in a sample of surgical patients with gastric and colorectal cancer. The mean duration of perioperative fasting was long (59 hours). Although fasting was not associated with the incidence of postoperative complications and death, a one-hour increase in perioperative fasting was associated with     19 However, nowadays, experts are contesting this type of conduct, because evidence has shown that early feeding can be administered with minimal risks and with potential benefits for patients. 20 The same has been described in relation to preoperative fasting, and there is a consensus in the literature regarding the importance of keeping this short. This is extremely important in populations such as that of the present study, with high frequency of diabetes (22%) and overweight (54.6%), as these individuals present the characteristics of oxidative stress and inflammation.
The mean duration of preoperative fasting was approximately 16 hours. This was longer than recommended, even in conserva- The results from the present study also show that non-survivor patients experienced a more prolonged duration of post and perioperative fasting. In the multivariate analysis, the durations of postoperative and perioperative fasting were probably not independent factors for mortality due to a lack of study power, given that the incidence of death was low in the current study. There is also a dearth of prospective studies about perioperative fasting focusing on selected outcomes (complications and mortality) among patients undergoing major surgery for cancer.
Receiving nothing orally for a long time preoperatively constitutes a persistent intervention and results in discomfort among patients. Clinical protocols should therefore be revised. 23 In a case study, 24 19 With the implementation of this protocol, the authors observed a significant decrease in the dura- This study has several limitations. First, the data collection method may have been a source of information bias since there is an element of subjectivity inherent in patient recall. It was also not possible to identify whether the fasting related only to medical prescription or whether the patients were unable to tolerate oral food, which probably related to the length of hospital stay. Second, the study was conducted in a single center and included patients with different cancer sites (heterogeneity of the study subjects and surgical procedures used). However, the baseline characteristics were not significantly different between the groups. Furthermore, the incidence of death in this sample was low, and it prevented us from performing multivariate analysis adjusted for confounders, in order to investigate the real association between perioperative fasting and mortality.
In addition, the study was conducted using a convenience sample and the analysis should be considered exploratory since the power of the study to test the hypothesis was not predefined. This matter needs to be better explored in further studies with larger samples.

CONCLUSION
Prolonged perioperative fasting was observed in this sample of patients with gastric and colorectal cancer and it was an independent predictor of the length of hospital stay. This result emphasizes that there is a need for protocols to shorten fasting in this group of patients.